scholarly journals My PCR: A Community Driven Approach to Raising Awareness About PCR in LMICs

2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 32s-32s
Author(s):  
Erin Lindsay Schneider ◽  
Pat Garcia-Gonzalez
Keyword(s):  
Conflicts Of Interest ◽  
Residual Disease ◽  
Disease Diagnosis ◽  
Local Context ◽  
Educational Materials ◽  
Advocacy Organizations ◽  
Raising Awareness ◽  
Polymerase Chain ◽  
The Impact ◽  
Educational Information

Abstract 49 Background: There is a significant need to increase awareness among chronic myeloid leukemia (CML) patients and their physicians about the importance of polymerase chain reaction (PCR) testing for disease diagnosis and monitoring. PCR is one of the most sensitive ways to diagnose CML and is one of the most reliable tools for monitoring disease. Many CML patients in LMICs lack access to PCR due to a lack of awareness and/or financial constraints. In 2012, My PCR was launched to address this. Goals: increase patient awareness of the importance of monitoring residual disease increase patient understanding of CML treatment milestones increase patients' involvement in treatment increase community awareness about needs of patients Methods: Led by The Max Foundation, My PCR is a coalition of 56 patient advocacy organizations from 51 countries (mostly LMICs) that uses a collaborative approach to raise awareness among stakeholders. My PCR provides educational information and resources in >25 languages, offers grants to partners to host booths at local and international hematology society conferences, host awareness events that engage physicians, and print educational materials. My PCR uses a website and social media to house resources and promote initiatives. Results: Since 2012, My PCR has: doubled its partnership base; reached over 40,000 patients, caregivers and physicians with educational information/resources, greatly increasing patient and physician understanding of PCR for CML monitoring in LMICs; and facilitated over 70 awareness events and regional meetings, bringing together patients and physicians to strengthen dialogue about CML treatment/monitoring. Next Steps: My PCR will create a PCR Advocacy Toolkit for advocates to adapt to their local context to increase access to PCR. The Toolkit will address how to collaborate with physicians, engage Ministries of Health, and utilize existing avenues for testing. Additionally, there will be an increased focus on measuring the impact of partners' efforts in improving access to PCR testing. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from either author.

The Addition of Thalidomide to the Induction Treatment of Newly Presenting Myeloma Patients Increases the CR Rate Which Is Likely to Translate Into Improved PFS and OS.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 352-352 ◽  
Author(s):  
Gareth J Morgan ◽  
Faith E Davies ◽  
Walter M Gregory ◽  
Susan E Bell ◽  
Alex J Szubert ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Response Rates ◽  
Multiparameter Flow Cytometry ◽  
Induction Treatment ◽  
Overall Response ◽  
Patient Pathways ◽  
The Impact

Abstract Abstract 352 We present updated results from MRC Myeloma IX study evaluating the role of the addition of thalidomide to the induction and maintenance of patients with myeloma. The study ran from May 2003 – November 2007 and randomised 1,970 patients and now has a median follow up of more than 3.5 years giving it improved power to detect changes in outcome developing later after treatment. Projected median OS younger fitter patients 66 months, median OS older less fit patients 32 months. The trial comprised of 2 patient pathways, one for younger fitter patients comparing CTD (cyclophosphamide, thalidomide, dexamethasone) with CVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone), all patients going on to receive an ASCT – median age 59 years. In older less fit patients, melphalan and prednisolone (MP) was compared to CTD attenuated – median age 73 years. In both pathways following initial treatment, eligible patients were randomised to low-dose thalidomide or no maintenance. Patient's response was monitored using electrophoresis, serum free light chain and multiparameter flow cytometry. Cytogenetics was availabel on up to 60% of cases and gene expression on a subset of these. CTD is a well tolerated regimen with a good safety profile giving excellent survivals in both groups of patients despite a small increase in risk of VTE. Using modified EBMT criteria, the addition of thalidomide to induction treatment increases both response rates and depth of response for all age groups. Preliminary results as follows: overall response: CTD vs CVAD: 91% v 82%; CR 21% v 14% and 100 days post-HDM, better responses were seen in CTD with CR rates 65% v 48%. Remission depth was also greater in CTD with more patients achieving minimal residual disease negativity by flow cytometry. The addition of thalidomide increases response rates overall, and particularly complete response (CR) rates (a 17% increase in CR rates post HDM, p=.006). In older/less fit patients CTDa vs MP: overall response 83% v 46%; CR 21% v 4%. Definitive results of these analyses will be presented as well as how they translate into PFS and OS and by cytogenetic subgroup. There is a substantial increase in response with the inclusion of thalidomide but at a median follow-up of three years we are not as yet seeing a substantial increase in survival in either of the two broad patient groups. We have collected data on treatment at relapse to explore how this confounds OS data. Importantly modelling analyses indicate when and to what extent, with further follow-up, the survival differences that should accrue from this increase in CR rate are likely to translate into a survival benefit. These results have a number of important implications. We show the benefit of the addition of thalidomide to myeloma treatment but also highlight the importance of later analysis of such trials because of the emergence of significant changes at these later time points. We will present full updated results from the study including the impact of thalidomide on cytogenetic subgroups and in the maintenance setting. Disclosures: No relevant conflicts of interest to declare.

Minimal Residual Disease Monitoring By Quantitative RT-PCR In t (8; 21) AML Early After Allogeneic HSCT Can Predict Clinical Outcomes and Allow Further Risk Stratification

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3386-3386
Author(s):  
Yu Wang ◽  
Yanrong Liu ◽  
Yazhen Qin ◽  
Xiao-Jun Huang
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Fusion Gene ◽  
Early Time ◽  
Preemptive Therapy ◽  
Clinical Relapse ◽  
Log Reduction ◽  
Multi Center Study ◽  
The Impact

Abstract Background Recent results from our prospective multi-center study identified patients with t (8; 21) AML as high-risk according to their MRD status after the second consolidation chemotherapy and allo-HSCT can benefit this part of patients; however, the relapse rate was reported to be 22% even after allo-HSCT for those high-risk patients. To date, there have been no studies to answer the question of whether the specific fusion gene, RUNX1/RUNX1T1 can be used to further distinguish between patients with low and high risks of relapse in allo-HSCT setting, just like the already established standard for MRD measurement in CML and APL. Methods Sixty consecutive AML patients with t (8; 21) and identified as high-risk according to the criteria from our recently published report patients who received allo-HSCT were enrolled between January 2006 and January 2013. Serial MRD monitoring by RQ-PCR post HSCT was done. The impact of MRD monitoring on transplant outcomes was assessed. Results A > 3 log reduction at 1 month after HSCT in RUNX1/RUNX1T1 transcripts from diagnosis, is associated with 2-year CIR of 17% in the 88% of patients achieving it, compared with 43% in the remaining (p=.02). A > 3 log reduction at 2 months after HSCT in transcripts from diagnosis, is associated with a CIR of 9% and LFS of 66% in the 86% of patients achieving it, compared with CIR of 100% and LFS of 0% in the remaining (both p<.001). A > 3 log reduction at 3 months after HSCT in RUNX1/RUNX1T1 transcripts from diagnosis, is associated with a CIR of 11% and LFS of 73% in the 78% of patients achieving it, compared with CIR of 44% and LFS of 0% in the remaining (both p<.001). Of the 60 patients analyzed, 28 patients had positive MRD, occurring at a median of 110 days (30-540 days) after transplant. The predictive value of sequential monitoring could be demonstrated in 8 patients culminating in clinical relapse (representing 73% of all relapsing patients). The median time from MRD positivity in BM to morphological relapse was 95 days (range, 33-140 days). Conclusions A > 3 log reduction at the first 3 months after HSCT in RUNX1/RUNX1T1 transcripts from diagnosis is highly prognostic. We conclude that MRD monitoring by RQ-PCR at regular early time points post HSCT in t (8; 21) AML allows further identification of patients at high risk of relapse even after allo-HSCT and could now be incorporated in clinical trials to evaluate the role of risk directed prophylactic/preemptive therapy. This work was partly supported by The Key Program of National Natural Science Foundation of China £¨Grant No. 81230013£©, Beijing Municipal Science & Technology Commission (No.Z121107002812033) and Bejing Municipal Science & Technology Commission£¨No.Z111107067311070). Disclosures: No relevant conflicts of interest to declare.

Impact Of Age On Toxicity Associated With Chemotherapy For Acute Lymphoblastic Leukaemia (ALL): Results From The UK Prospective Study UKALL2003

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 840-840
Author(s):  
Rachael E. Hough ◽  
Clare Rowntree ◽  
Rachel Wade ◽  
Nicholas Goulden ◽  
Chris Mitchell ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Residual Disease ◽  
Age Groups ◽  
Serious Adverse Events ◽  
Number Of Patients ◽  
Teenagers And Young Adults ◽  
The Uk ◽  
Cure Rates ◽  
The Impact

Abstract Despite the substantial improvements made in the outcomes of paediatric ALL, with ‘cure' rates now in excess of 90%, survival in teenage and young adult (TYA) patients has remained inferior. The reasons for this are likely multifactorial, including tumour biology, toxicity, compliance, access to clinical trials and protocol (adult or paediatric) used. We report the toxicity profiles observed in children, teenagers and young adults treated on the UK intensive, minimal residual disease (MRD) directed ALL protocol, UKALL2003. Of a total of 3126 patients treated, 1520 patients were under 5 years old, 767 were aged 5-9 years, 610 aged 10-15 years and 229 aged 16-24 years, with a median overall follow-up of 4 year and 10 months. The risk of serious adverse events (SAEs) was higher in patients older than 10 years (56% in 10-15 year olds, 53% in 16-24 year olds) compared to those aged 9 or younger (30% in under 5 years and 31% in 5-9 years)(p<0.0001), with no difference in the those aged 16-24 compared to younger teenagers (p=0.5). The incidence (per number of patients in each group) and distribution of toxicities according to age group is summarised in the table.Table 1Age in years<55-910-1516-24AllTotal number of patients1520767610229 NB: 56 pts≥20 years3126Infection n (%)328 (21.6%)130 (17.0%)145 (23.8%)72 (31.4%)675 (21.6%)Asaparaginase n (%)57 (3.8%)57 (7.4%)64 (10.5%)31 (13.5%)209 (6.7%)Methotrexate n (%)100 (6.6%)74 (9.6%)123 (20.2%)33 (14.4%)330 (10.6%)Steroid n (%)54 (3.6%)37 (4.8%)141 (23.1%)52 (22.7%)284 (9.0%)Vincristine n (%)34 (2.2%)11 (1.4%)22 (3.6%)7 (3.0%)74 (2.4%)Other SAEs94 (6.2%)42 (5.5%)90 (14.8%)25 (10.9%)251 (8.0%) The incidence of certain toxicities including viral infection (5.3%), asparaginase hypersensitivity (1.9%) and vincristine neurotoxicity (2.1%) appeared equivalent across all age groups. Avacular necrosis was seen predominantly in adolescents (83% of 147 events in 10-19 year olds) and was rare in those younger than 10 years (n=18) or older than 20 years (n=7). Asparaginase thrombotic events increased in frequency with increasing age (1.5% in under 5 years, 3.3% in 5-9 years, 4.4% in 10-15 years and 8.3% in 16-24 year olds)(p<0.0001). All other toxicities were more frequently observed in over 10 year olds compared to patients aged 9 or younger, with no difference between 16-24 year olds and 10-15 year olds. The impact of age on SAEs associated with intensive ALL chemotherapy varies according to specific toxicities. In general, toxicity is higher in those over 10 years compared to younger patients, with no excess toxicity in those aged 16-24 compared to 10-15 years. However, specific toxicities may increase with increasing age (thrombosis), be restricted to adolescence (AVN) or be unrelated to age (vincristine neurotoxicity, asparaginase hypersensitivity). Disclosures: No relevant conflicts of interest to declare.

scholarly journals Preventive Effects of Cardotoxicities By Liposomal Anthracyclines non Pegilated in 95 Perspective Patients Affected By Lymphoma and Monitored By Biomarkers and Ecocardiography

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5433-5433
Author(s):  
Guido Gini ◽  
Jacopo Olivieri ◽  
Caterina Bocci ◽  
Michela Sampaolo ◽  
Silvia Trappolini ◽  
...  
Keyword(s):  
Troponin I ◽  
Cardiac Toxicity ◽  
Conflicts Of Interest ◽  
Final Analysis ◽  
Disease Diagnosis ◽  
Therapeutic Interventions ◽  
Resource Saving ◽  
Monitoring Method ◽  
The Impact

Abstract Anthracyclines (AC) still constitute the mainstay of the 1st line treatment in lymphoma: their use, however, is limited by the occurrence of Cardiac Toxicity (CT). The exact prevalence of AC CT occurring after widely used regimens such as R-CHOP or ABVD is unknown and there is uncertainty about the best monitoring method and possible prophylactic or therapeutic interventions. METHODS: We started a prospective observational trial in lymphoma patients undergoing treatment with conventional or liposomal AC. We used a comprehensive approach to monitor for AC CT, using a telemedicine(TM) system integrating echocardiography, ECG and biomarkers (Troponin I - TnI). RESULTS: In this final analysis, 95 patients completed the planned treatment (52 males and 43 females). Median age was 56.03 years (range 19.1 to 78.5 years), and 36 patients were > 65 years. 23 were HL and 72 NHL (DLBCL was the most represented subtype with 47 cases). Liposomal AC was used in 31 patients and classical AC in 64, with mean cumulative doses of 283.33 and 272.76 mg/sqm, respectively. 10/95 patients (11%) developed a TnI rise above 0.08 ng/ml and 39/95 (41%) above 0.03 ng/ml. With both cut-offs, the rises occurred more frequently at cumulative doses >200 mg/sqm. The major arising occurred in the group underwent classical AC, while in the group underwent liposomal AC although the value before first infusion was in 10% more than 0.03 at the cumulative dose of 300 mg /sqm there's a plateau of troponin value. Thanks to this monitoring system we noticed 2 Acute cardiac toxicity events with resolution in 100% of cases. Furthermore in those cases where has registered a subclinical CT has begun a prompt Cardiological therapy by ACE inhibitors and Beta Blocker to reduce the relative risk of Cardiological events. CONCLUSIONS: Even with low cumulative doses, with a median follow up of 13 months, subclinical signs of AC CT were found in at least 11% of patients. The use of liposomal AC allow the safe treatment of patients with a previous heart disease diagnosis rather it seem protective in the higher cumulative doses. A longer follow up will be able to clarify the impact of arising of TnI more than 0.03 and 0.08 on the developing of AC CT in all our series. On the basis of our experience a multicentric trial has begun on behalf Italian Lymphoma Foundation (FIL) In a low-risk setting for AC CT, a monitoring strategy combining clinical, imaging, instrumental and biomarker data seems to enhance the sensitivity of separate methods. This strategy is feasible and resource-saving thanks to the integration in a TM system. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

IDH Mutations Identify a Subgroup of NPM1 Patients with a More Favorable Prognosis. a Retrospective Multicenter Study of the Filo Group

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Sylvain Garciaz ◽  
Marie Anne Hospital ◽  
Colombe Saillard ◽  
Yosr Hicheri ◽  
Evelyne D'Incan ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Residual Disease ◽  
Complete Response ◽  
Response To Treatment ◽  
P Value ◽  
High Dose ◽  
Idh Mutation ◽  
Npm1 Mutation ◽  
Idh Mutations ◽  
The Impact

IDH mutations are strongly enriched in cytogenetically normal AML harboring NPM1 mutation (CN-NPM1mut-AML). The impact of these mutations on response to treatment is still a matter of debate. In the ELN 2017 classification, NPM1mut/FLT3-ITD allelic ratio &gt;0.5 (FLT3-high) are considered intermediate-risk AML, whereas NPM1mut/ FLT3-ITD neg or &lt;0.5 (FLT3-low) are low-risk. We aimed to evaluate the impact of IDH mutation in CN-NPM1mut-AML patients (pts) treated intensively. For this purpose, we retrospectively analyzed 177 CN-NPM1-AML pts from the Paoli-Calmettes Institute and from the French Innovative leukemia organization (FILO) databases who had received conventional intensive chemotherapy according to the FILO protocols (anthracycline-cytarabine based regimen for induction and High-intermediate dose cytarabine (HIDAC) for consolidation. Forty-seven (26%) AML pts had an IDH mutation -18 IDH1-R132 (10%), 27 IDH2-R140 (15%) and 2 IDH2-R172 (1%) - while 130 AML pts were IDHwt. Pts characteristics are presented in the Table.The complete response rate after one or two courses of chemotherapy (CR1) was 100% and 90% (p-value=.03) in the IDHmut and IDHwt groups, respectively. For pts in CR1, NPM1 molecular residual disease after the first consolidation (MRD2) was negative (&gt;4 Log reduction) in 86% vs 53% of pts (p-value=.04). Nine (19%) and 24 (18%) pts received an allogeneic transplantation in CR1. The median time between CR1 and relapse was 11 months and 8 months, in IDHmut and IDHwt pts, respectively (p-value=.008). Day-100 non-relapse mortality was 8% and 12% respectively (p-value=ns). Median follow-up is 45 months (range, 2.4-115). Median EFS and OS are 21 months vs 12 months (p-value=.01) and 112 vs 23 months (p-value=.02), in the IDHmut vs IDHwt groups respectively (Figure). No survival differences were observed between IDH1mut and IDH2mut AML patients. Multivariate analyses with age&gt;65, FLT3-high and IDHmut as covariates showed that IDHmut was independently associated with a higher EFS (HR=1.7, ranges 1.1-2.6) and OS (HR=1.7, ranges 1.1-2.7). Our results suggest that IDHmut is associated with a better response and a good disease control with high-dose chemotherapy. Nevertheless, some relapses still occur justifying the use of an IDH inhibitor combined with first-line chemotherapy or in a post-remission maintenance setting. Figure Disclosures No relevant conflicts of interest to declare.

Comparison of Molecular Kinetics after the First and Second Imatinib Discontinuation: Results from the KID Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1920-1920
Author(s):  
Dae Young Zang ◽  
Sung-Eun Lee ◽  
Soo Young Choi ◽  
Soo-Hyun Kim ◽  
So-Young Park ◽  
...  
Keyword(s):  
Median Duration ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Chronic Phase ◽  
Intermittent Therapy ◽  
Molecular Response ◽  
Polymerase Chain ◽  
Multicenter Prospective Study ◽  
Treatment Free Remission

Abstract Backgroud: Recent reports showing that imatinib (IM) discontinuation can be employed in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation result in treatment-free remission (TFR) as a new therapeutic goal in chronic phase chronic myeloid leukemia (CP CML). Although 50-70% of patients experienced molecular relapse by several TFR studies, the most of patients resumed molecular responses (MR) following restart of IM. Through the Korean multicenter prospective study (Korean Imatinib Discontinuation Study; KID Study), we have identified predictors for sustained UMRD and explored molecular kinetics after the first IM discontinuation. In patients regaining durable UMRD with IM resumption, we tried second IM discontinuation and compared molecular kinetics between the first IM stop and second IM stop. Methods: CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results: By the data cut-off date of 31 July 2015, among 90 non-transplant UMRD patients with at least 12 months of follow-up, 37 patients lost MMR in 2 consecutive analyses and resumed IM. Among them, 9 patients (5 men and 4 women) with a median age of 54 years (range, 35-59 years) entered into a second IM discontinuation after maintaining UMRD at least 2 years. Prior to first discontinuation, the median duration of IM therapy was 76.8 months (range, 38.5-129.0 months) and the duration of sustained UMRD was 30.1 months (range, 24.4-64.5 months). After first attempt of IM discontinuation, they relapsed after a median duration of 3.7 months (range, 1.9-20.8 months) and re-achieved UMRD at a median of 5.5 months (range, 1.8-9.4 months) after IM resumption. After sustaining a second UMRD for a median of 25.7 months, IM therapy discontinued for a second time. After a median follow-up of 37.4 months (range, 19.7-58.5 months) after second IM discontinuation, 7/9 patients (78%) and 4/9 patients (44%) lost UMRD and MMR, respectively. Among three patients who lost UMRD but not MMR, one patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for 19.5 months and two patients has not yet been followed up after a first detection of UMRD loss. Four patients who experienced second relapse (MMR loss) after a median 2.9 months (range, 2.7-3.9 months), which was similar to those of the first IM discontinuation [median 3.75 (range, 1.9-3.9 months)]. The patients who lost MMR were retreated with IM for a median of 13.6 months (range, 0.8-18.6 months); three patients re-achieved MMR at 3.5, 5.5, and 11.5 months, respectively and one re-achieved UMRD at 7.2 months. Conclusion: Our data demonstrated that a second attempt might be possible and the median time to MMR loss after second discontinuation was similar to those of the first discontinuation. But the molecular kinetics after second IM resumption needs longer follow-up with more patients. Further studies on the predictors to select patients for a trial of second TFR and novel strategies such as intermittent therapy will be warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial

2021 ◽  
Vol 5 (17) ◽  
pp. 3322-3332
Author(s):  
Rachel J. Mitchell ◽  
Amy A. Kirkwood ◽  
Emilio Barretta ◽  
Laura Clifton-Hadley ◽  
Emma Lawrie ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Dominant Negative ◽  
Data Sets ◽  
Loss Of Function ◽  
Free Survival ◽  
Multivariable Analyses ◽  
Polymerase Chain ◽  
The Impact ◽  
Dependent Probe

Abstract IKZF1 deletions (ΔIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect ΔIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL1+ and BCR-ABL1− B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) Δ4-7 or the loss of function Δ2-7, Δ4-8, and Δ2-8 (n = 498), MLPA (n = 436), or by both (n = 420). Although patients with BCR-ABL1− ΔIKZF1 were more likely to have minimal residual disease at the end of induction, we did not find any impact of ΔIKZF1 (including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between ΔIKZF1 and outcome is the older age of participants in our population. The impact of ΔIKZF1 in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.gov as #NCT01085617.

scholarly journals Boosting Immunity against Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1221
Author(s):  
Raquel Lopes ◽  
Bruna Velosa Ferreira ◽  
Joana Caetano ◽  
Filipa Barahona ◽  
Emilie Arnault Carneiro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Proteasome Inhibitors ◽  
Treatment Strategies ◽  
Complete Response ◽  
Drug Conjugates ◽  
Incurable Disease ◽  
Car T ◽  
Patient’S Outcome ◽  
The Impact

Despite the improvement of patient’s outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody–drug conjugates or bispecific antibodies broadened the possibility of improving patients’ survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

scholarly journals Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Parp Inhibition ◽  
High Risk Population ◽  
Risk Population ◽  
The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

scholarly journals Cultural and Creative Cities and Regional Economic Efficiency: Context Conditions as Catalyzers of Cultural Vibrancy and Creative Economy

2021 ◽  
Vol 13 (13) ◽  
pp. 7150
Author(s):  
Silvia Cerisola ◽  
Elisa Panzera
Keyword(s):  
Fixed Effects ◽  
Local Context ◽  
Creative Economy ◽  
Fixed Effects Model ◽  
Creative Cities ◽  
Economic Output ◽  
Innovative Methodology ◽  
Holistic Conception ◽  
Panel Fixed Effects ◽  
The Impact

Following the hype that has been given to culture and creativity as triggers and enhancers of local economic performance in the last 20 years, this work originally contributes to the literature with the objective of assessing the impact of cultural and creative cities (CCCs) on the economic output of their regions. In this sense, the cultural and creative character of cities is considered a strategic strength and opportunity that can spillover, favoring the economic system of the entire regions in which the cities are located. Through an innovative methodology that exploits a regional production function estimated by a panel fixed effects model, the effect of cities’ cultural vibrancy and creative economy on the output of their regions is econometrically explored. The data source is the Cultural and Creative Cities Monitor (CCCM) provided by the JRC, which also allows the investigation of the possible role played by the enabling environment in catalyzing the action of cultural vibrancy and creative economy. The results are thoroughly examined: especially through cultural vibrancy, CCCs strategically support the output of their region. This is particularly the case when local context conditions—such as human capital and education, openness, tolerance and trust, and quality of governance—catalyze their effect. Overall, CCCs contribute to feeding a long-term self-supporting system, interpreted according to a holistic conception that includes economic, social, cultural, and environmental domains.

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